title: Effects of maternal immune activation on adult neurogenesis in the subventricular zone-olfactory bulb pathway and olfactory discrimination.
abstract: Maternal infection and maternal immune activation (MIA) during pregnancy increase risks for psychiatric disorders such as schizophrenia and autism. Many deficits related to psychiatric disorders are observed in adult offspring of MIA animal models, including behavioral abnormalities, morphological defects in various brain regions, and dysregulation of neurotransmitter systems. It has previously been shown that MIA impairs adult neurogenesis in the dentate gyrus of the hippocampus. In this study, we examined whether MIA affects adult neurogenesis in the subventricular zone (SVZ)-olfactory bulb (OB) pathway. Polyinosinic-polycytidylic acid (PolyI:C), a synthetic analog of double-stranded RNA mimicking viral infection, was injected into pregnant mice on gestation day 9.5 to activate immune systems. In the SVZ-OB pathway of adult offspring, different cell types of the neural stem cell lineage responded differently to MIA. Neural stem cells and neuroblasts were decreased. Cell proliferation of transit-amplifying cells was impaired. Consequently, newborn neurons were reduced in the OB. Olfactory deficiency has been suggested as a biomarker for schizophrenia. Here we found that olfactory discrimination was compromised in adult MIA offspring. Taken together, these findings show that MIA leads to defective adult neurogenesis in the SVZ-OB pathway, and the impairment of adult neurogenesis may lead to deficits in olfactory functions.
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Yuan-Hsuan
authors.initials: YH
authors.lastname: Liu
authors.forename: Wen-Sung
authors.initials: WS
authors.lastname: Lai
authors.forename: Huey-Jen
authors.initials: HJ
authors.lastname: Tsay
authors.forename: Tsu-Wei
authors.initials: TW
authors.lastname: Wang
authors.forename: Jenn-Yah
authors.initials: JY
authors.lastname: Yu
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002552:Cerebral Ventricles / Q000473:pathology*; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D009830:Olfactory Bulb / Q000187:drug effects / Q000473:pathology*; D009833:Olfactory Pathways / Q000187:drug effects / Q000473:pathology*; D011070:Poly I-C / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000473:pathology*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D012903:Smell / Q000187:drug effects / Q000276:immunology / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D011070:Poly I-C; D055748:SOXB1 Transcription Factors; C499317:Ascl1 protein, mouse; C527783:Sox2 protein, mouse
keywords: Adult neurogenesis; Olfaction; Olfactory bulb; Prenatal immune activation; Schizophrenia; Subventricular zone